Preventing transition "regret": An institutional ethnography of gender-affirming medical care assessment practices in Canada.

When a person openly "regrets" their gender transition or "detransitions" this bolsters within the medical community an impression that transgender and non-binary (trans) people require close scrutiny when seeking hormonal and surgical interventions. Despite the low prevalence of "regretful" patient experiences, and scant empirical research on "detransition", these rare transition outcomes profoundly organize the gender-affirming medical care enterprise. Informed by the tenets of institutional ethnography, we examined routine gender-affirming care clinical assessment practices in Canada. Between 2017 and 2018, we interviewed 11 clinicians, 2 administrators, and 9 trans patients (total n = 22), and reviewed 14 healthcare documents pertinent to gender-affirming care in Canada. Through our analysis, we uncovered pervasive regret prevention techniques, including requirements that trans patients undergo extensive psychosocial evaluations prior to transitioning. Clinicians leveraged psychiatric diagnoses as a proxy to predict transition regret, and in some cases delayed or denied medical treatments. We identified cases of patient dissatisfaction with surgical results, and a person who detransitioned. These accounts decouple transition regret and detransition, and no participants endorsed stricter clinical assessments. We traced the clinical work of preventing regret to cisnormativity and transnormativity in medicine which together construct regret as "life-ending", and in turn drives clinicians to apply strategies to mitigate the perceived risk of malpractice legal action when treating trans people, specifically. Yet, attempts to prevent these outcomes contrast with the material healthcare needs of trans people. We conclude that regret and detransitioning are unpredictable and unavoidable clinical phenomena, rarely appearing in "life-ending" forms. Critical research into the experiences of people who detransition is necessary to bolster comprehensive gender-affirming care that recognizes dynamic transition trajectories, and which can address clinicians' fears of legal action-cisgender anxieties projected onto trans patients who are seeking medical care.

Menopause, Reproductive Life, Hormone Replacement Therapy, and Bone Phenotype at Age 60-64 Years: A British Birth Cohort.

CONTEXT: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment. OBJECTIVE: The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60-64 years. DESIGN: This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. SETTING: The study was conducted in England, Scotland, and Wales. PARTICIPANTS: Participants included 848 women with a known type of menopause and bone measures at 60-64 years. MAIN OUTCOME MEASURES: Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured. RESULTS: A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%-15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%-11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%-9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%-1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography. CONCLUSIONS: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI and aBMD.

Gene expression profiles of hair and wool sheep reveal importance of Th2 immune mechanisms for increased resistance to.

Management of gastrointestinal parasites is a critical issue for sheep producers worldwide. Increases in the prevalence of drug-resistant worms have complicated parasite control and increased economic losses. Therefore, other methods of parasite control need to be assessed, including the use of genetically resistant animals in breeding programs. Hair sheep breeds such as the St. Croix have greater parasite resistance than conventional wool breeds. However, the immune mechanisms that control parasite resistance in hair or wool breeds have not yet been fully determined, and information on cytokine expression profiles for both wool sheep selected for increased resistance and hair sheep is limited. Our objective was to investigate gene expression differences in 24 parasite-resistant hair and 24 susceptible wool sheep to identify immune effectors associated with resistance to . One-half of the lambs were infected and sacrificed at 3 or 27 d after infection. Remaining lambs were not infected. Breed differences in expression of genes associated with Th1 and Th2 immune responses in lymph nodes and abomasal tissue were determined. Th2-associated genes included IL-4, IL-13, IL-5, IgE, the α chain of the IL-4 receptor, and the α chain of the high-affinity IgE receptor (FcεRI). Th1-associated genes included interferon gamma (IFN-γ), the p35 subunit of IL-12 (IL-12 p35), and the ß1 and ß2 chains of the IL-12 receptor (IL-12 Rß1 and IL-12 Rß2, respectively). In both hair and wool sheep, infection with resulted in greater expression of IgE, IL-13, IL-5, and IL-12 p35 and somewhat reduced expression of IFNγ in lymph nodes. In abomasal tissue, parasite infection resulted in greater IgE, IL-13, FcεRI, and IL-12 p35 expression in infected lambs compared with control lambs. Between breeds, hair sheep had a stronger Th2 response after infection than wool sheep, with increased expression of IgE and IL-13 and decreased expression of IFNγ in lymph nodes and increased expression of IL-13 and decreased expression of IL-12 p35 in abomasal tissue. Expression of IL-4 in lymph nodes did not differ between hair and wool lambs, and IL-4, IL-5, IL-12 Rß1, and IL-12 Rß2 expression was too low to measure at the times sampled in abomasal tissue.

Longitudinal fecal hormone analysis for monitoring reproductive activity in the female polar bear (Ursus maritimus).

The objective was to identify suitable enzyme immunoassays to monitor gonadal and placental function in the female polar bear. Immunoreactive progesterone, progesterone metabolite (PdG), estrogen, and androgen metabolite (T) concentrations were measured in fecal samples collected over 24 mo from captive female bears (N = 20). Whereas fecal extracts produced displacement curves parallel to the standard curve for each respective steroid, T and PdG more accurately reflected reproductive events. Concentrations of fecal T increased (P < 0.05) during the breeding season, and brief spikes were associated with estrus and mating. A postovulatory increase in PdG was not always detected, but sustained baseline T after mating appeared consistent with ovulation. Parturient bears excreted higher PdG concentrations (P < 0.05) during expected time of embryo implantation in Fall, and a late gestational rise in fecal T occurred 30 days prepartum. Many nonparturient bears also had a PdG rise in the Fall, suggesting they experienced either pregnancy loss or a pseudopregnancy. Differentiating pregnant and pseudopregnant states was not achieved using fecal PdG alone, but when combined with fecal T, comprehensive diagnoses could be made. Nonparturient bears demonstrated elevated (P < 0.05) fecal T during summer months, whereas parturient bears did not. In summary, noninvasive hormone monitoring techniques were established for the female polar bear. Although this study was directed at facilitating management and breeding efforts of captive polar bears, the methods could be applied to studies of reproductive function in wild populations.

Factors influencing annual fecal testosterone metabolite profiles in captive male polar bears (Ursus maritimus).

The objectives of this study were to assess the effects of season, breeding activity, age and latitude on fecal testosterone metabolite concentrations in captive, adult male polar bears (Ursus maritimus). Fourteen polar bears from 13 North American zoos were monitored for 12-36 months, producing 25-year-long testosterone profiles. Results indicated that testosterone was significantly higher during the breeding season (early January through the end of May) compared with the non-breeding season with the highest concentrations excreted from early January through late March. Variations in excretion patterns were observed among individuals and also between years within an individual, with testosterone peaks closely associated with breeding activity. Results indicate that fecal testosterone concentrations are influenced by season, breeding activity and age, but not by latitude. This is the first report describing longitudinal fecal testosterone metabolite concentrations in individual adult male polar bears.

Field primatology of today: current ethical issues.

As members of professional organizations such as American Society of Primatologists (ASP) and the International Primatological Society (IPS), primatologists must adhere to a set of nonhuman primate-focused principles outlined in resolutions and policy statements on, for example, the ethical treatment of nonhuman primates. Those of us that work in the field must also address issues such as the protection of primate health in the wild and the conservation of wild primate populations. Moreover, we increasingly find ourselves in complex situations where we must balance human and nonhuman primate needs and interests. The selection of commentary pieces in this edition of the American Journal of Primatology originated from presentations given in the symposium, Field Primatology of Today: Navigating the Ethical Landscape, held at the 32nd Annual Meeting of the American Society of Primatologists (ASP) in September 2009. The goals of that symposium and these resulting commentary pieces are threefold: (1) to revive a discussion of key contemporary ethical issues faced by field primatologists, (2) to highlight the need for centrally placed ethical considerations in various facets of our professional lives, particularly research and teaching, and (3) to consider what a comprehensive ethical code that addresses all of these issues might look like.

Differences in immune parameters are associated with resistance to Haemonchus contortus in Caribbean hair sheep.

Caribbean hair sheep are more resistant to gastrointestinal nematodes than conventional wool breeds, but mechanisms that confer resistance are not fully understood. This study compared immune effector cell populations and antibody concentrations in 12 hair and 12 wool lambs infected with the abomasal parasite Haemonchus contortus and sacrificed at 3 or 27 days post-infection (p.i.) and 14 uninfected animals of each breed. Faecal egg counts were over 2.5-fold higher (P = 0.12) and packed cell volumes approximately 8% lower (P < 0.10) in infected wool lambs. Abomasal lymph nodes were heavier in infected animals (P < 0.05) and infected hair sheep had larger lymph nodes than infected wool sheep (P < 0.05). Tissue eosinophil concentrations were likewise larger (P = 0.07) in hair compared with wool sheep at 3 days p.i. Circulating levels of IgE and IgA in uninfected lambs were higher in hair sheep (P < 0.05) and during infection, hair sheep had higher serum IgA than wool sheep at 3, 5, and 21 days p.i. (P < 0.05). Serum IgE in infected lambs did not differ between breeds, but concentrations of IgE in lymph nodes were higher (P < 0.01) at 27 days p.i. in infected hair sheep.

One hundred questions of importance to the conservation of global biological diversity.

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.

Microarray analysis reveals difference in gene expression profiles of hair and wool sheep infected with Haemonchus contortus.

Sheep infected with the abomasal parasite, Haemonchus contortus, have reduced growth rates, decreased wool production, and anemia, and heavy infections may result in death. Anthelmintic treatment can remove worms, but the cost of treatment and prevalence of drug-resistant worms has led to greater focus on genetic resistance of the host to parasitism. Variation in parasite resistance exists within and among sheep breeds, and Caribbean hair sheep have greater resistance than most conventional wool breeds. Our objective was to investigate differences in gene expression between 24 parasite-resistant hair and 24 susceptible wool lambs to determine genetic mechanisms involved in resistance to H. contortus. Half of the animals of each breed were infected and sacrificed at 3 or 27 days post-infection; the remaining animals were uninfected controls. Breed differences in abomasum and abomasal lymph node tissue gene expression were assessed using bovine cDNA microarrays. Over 60 transcripts differed between breeds for each tissue and infection status. Genes differentially expressed between hair and wool sheep 3 days PI were assessed for gene function and mechanisms for greater immune cell infiltration, abomasal tissue repair, Th17 response, and anticoagulation were present in parasite-resistant hair sheep. By 27 days PI, hair sheep had greater expression of genes involved in gut motility, inflammatory cytokines, and cell proliferation and differentiation compared to wool sheep. Changes in these processes indicate Caribbean hair sheep have a stronger inflammatory response when infected with H. contortus which may facilitate the increased parasite resistance observed in these sheep.

Expression profile of toll-like receptors within the gastrointestinal tract of 2-day-old Salmonella enteriditis-infected broiler chickens.

Salmonella enterica serovar Enteriditis (SE) causes a majority of foodborne illness in the U.S. A more productive avian innate immune response could reduce bacterial colonization and the incidence of infection in humans. However, quantification and comparison of the toll-like receptors (TLR), a component of the innate immune system that recognize bacterial pathogens, and their response to SE colonization across the avian gastrointestinal (GI) tract has not been reported. Therefore, we assessed these changes using real-time qRT-PCR to measure expression of TLR 1LA, 2A, 2B, 3, 4, 5, 7, 15, and 21 in the duodenum, jejunum, ileum, cecal tonsil, ceca, and large intestine of uninfected and SE-infected 2-day-old broiler chickens. Samples were collected soon after hatch to approximate natural SE exposure and to measure initial changes in the immune response to infection. All TLRs had measurable expression within the duodenum, jejunum, ileum, cecal tonsil, ceca, and large intestine. The general expression pattern, with the exception of TLR 21, showed distal GI segments had higher TLR mRNA expression than proximal segments. Infected chickens had increased expression of TLR 1LA, 2A, 4, and 15 in distal GI segments and upregulation of TLR 2B, 3, and 15 in proximal segments, including the duodenum. Interestingly, SE-infection caused downregulation of TLR 5, with no change in TLR 7 or 21. Overall, we provide a comprehensive report of mRNA expression profiles for the TLR family of innate immune receptors in the GI tract of 2-day-old broilers and their differential response to SE colonization.

In ovo treatment with CpG oligodeoxynucleotides decreases colonization of Salmonella enteriditis in broiler chickens.

Induction of the innate immune response in newly hatched chickens is important for limiting infections with bacteria, such as Salmonella enterica serovar Enteriditis (SE). CpG oligodeoxynucleotides (CpG-ODN) can stimulate the innate immune response of young chickens. Therefore, we examined the effectiveness of CpG-ODN administered in ovo on intestinal colonization by SE and the ability to modulate the function of heterophils in young chickens. Heterophils were isolated from 2-day-old chickens and were stimulated with heat-killed SE (HK-SE) or PMA for oxidative burst and HK-SE or live SE for degranulation assays. CpG-ODN treatment had no effect on heterophil oxidative burst when stimulated with HK-SE or PMA. However, HK-SE and live SE increased degranulation (P<0.01) in heterophils from CpG-ODN-treated birds compared to PBS-treated controls. In a second experiment, chickens were orally infected with SE on day 10 post-hatch and cecal contents were collected 6 days later for assessment of SE intestinal colonization. CpG-ODN treatment reduced SE colonization by greater than 10-fold (P<0.001) compared to PBS-injected control birds. Overall, we show for the first time that CpG-ODN given in ovo stimulates innate immune responsiveness of chicken heterophils and increases resistance of young chickens to SE colonization.

Protein C and protein S levels can be accurately determined within 24 hours of diagnosis of acute venous thromboembolism.

In the 50% of cases of acute idiopathic venous thromboembolism, laboratory testing for inherited causes is often performed. Most physicians are under the impression that assays for protein C and protein S should not be measured at the time of diagnosis because of a high false positive rate. We performed a prospective cohort study from two outpatient thromboembolism clinics on consecutive patients with an objectively confirmed diagnosis of first acute idiopathic venous thromboembolism. Assays for protein C and protein S were performed prior to the initiation of oral anticoagulation therapy and within 24 h of diagnosis of venous thromboembolism. Abnormal results were repeated when patients discontinued oral anticoagulant therapy. Of 253 patients tested for both protein C and protein S, 229 (91%; 95% confidence interval 87-94%) were negative and 484 of 508 (95%) tests were normal. Of the 24 initial abnormal results, 21 were repeated and 10 (48%; 95% confidence interval 26-70%) were still abnormal. Overall, 97.8% of initial protein C and protein S results were accurate. If protein C and protein S are measured at the time of diagnosis of acute venous thromboembolism, the majority of the results will be normal and false positives are uncommon.

Effect of 3.2 vs. 3.8% sodium citrate concentration on anti-Xa levels for patients on therapeutic low molecular weight heparin.

In this study, we compared the effect of sodium citrate, a sample collection variable, on the anti-Xa levels of patients (n = 28) on dalteparin, a low molecular weight heparin. The median anti-Xa level for 3.2% sodium citrate was 0.235 U/ml while the median level for 3.8% sodium citrate was 0.230 U/ml. We conclude that different sodium citrate concentrations give statistically equivalent anti-Xa levels for the same samples. This conclusion is in contrast to the findings of the effect of sodium citrate concentration on International Normalized Ratio (INR) and activated partial-thromboplastin time (aPTT). In accordance with previous recommendations, we advocate the exclusive use of 3.2% sodium citrate in an effort to standardize coagulation testing.

A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism.

We compared three rapid D-dimer methods for the diagnosis of venous thromboembolism. Patients presenting to four teaching hospitals with the possible diagnosis of deep vein thrombosis or pulmonary embolism were investigated with a combination of clinical likelihood, D-dimer (SimpliRED) and initial non-invasive testing. Patients were assigned as being positive or negative for deep vein thrombosis or pulmonary embolism based on their three-month outcome and initial test results. The three D-dimer methods compared were: (a) Accuclot D-dimer (b) IL-Test D-dimer (c) SimpliRED D-dimer. Of 993 patients, 141 had objectively confirmed deep vein thrombosis or pulmonary embolism. The sensitivity of SimpliRED, Accuclot and IL-Test were 79, 90 and 87% respectively. All three D-dimer tests gave similar negative predictive values. The SimpliRED D-dimer was found to be less sensitive than the Accuclot or IL-Test. When combined with pre-test probability all three methods are probably acceptable for use in the diagnosis of venous thromboembolism.

Use of microalbuminuria as a predictor of outcome in critically ill patients.

We have investigated the use of microalbuminuria as a predictor of outcome in a pilot study involving 50 critically ill patients in a six-bed hospital intensive care unit (ICU). Urinary microalbumin:creatinine (M:Cr) ratios measured only 6 h after admission to the ICU demonstrated a significant difference (P = 0.01) between survivors and non-survivors, allowing rapid identification of patients at increased risk of developing organ failure and at greater risk of death. This work suggests that earlier identification of these patients using a rapid, simple, inexpensive biochemical test is possible; if confirmed in a larger study, it may be that clinical interventions can be targeted at those most likely to benefit.

Measures of total free radical activity in critically ill patients.

OBJECTIVES: To examine the role played by free radicals during the initial phase of critical illness in patients on an Intensive Care Unit (ICU). DESIGN AND METHODS: Serum total antioxidant status (TAS) and uric acid (UA) levels were measured in 50 patients over 18 hours to represent the initial stage of critical illness. Clinical scoring systems (APACHE II and multiple organ dysfunction scores) were used to assess the degree of organ dysfunction. Outcome was assessed according to patient survival (survivors, n = 36; non-survivors, n = 14). RESULTS: Serum TAS was higher in non-survivors; a similar finding was demonstrated for serum UA. Levels of both biochemical markers were associated with the degree of organ function and with higher antioxidant and UA levels present in patients with more severe organ dysfunction. In addition, serum UA was significantly correlated to serum TAS and probably accounted for much of the antioxidant activity observed. CONCLUSIONS: The increased TAS and UA levels observed may simply be a response to the degree of renal dysfunction observed as those patients with worse renal function had higher TAS and UA levels. In conclusion, measurement of serum TAS appears to be a reflection of UA concentration and results should be interpreted with caution particularly in patients who have renal dysfunction.

Three different chromogenic methods do not give equivalent anti-Xa levels for patients on therapeutic low molecular weight heparin (dalteparin) or unfractionated heparin.

In this study we compare three chromogenic methods (IL-Heparin, Stachrom Heparin and Heparin Sigma) on two different instruments (ACL300+ and AMAX CS190) for patients on dalteparin (n = 41), a low molecular weight heparin or unfractionated heparin (n = 50). For dalteparin the mean anti-Xa levels for IL-Heparin, Stachrom Heparin and Heparin Sigma were 0.27, 0.30 and 0.21 U/ml, respectively, while for heparin they were 0.52, 0.55 and 0.41 U/ml, respectively. To test for instrument specific effects, IL-Heparin and Stachrom Heparin were repeated on both instruments on 42 patients receiving unfractionated heparin. For IL-Heparin the mean anti-Xa levels on the AMAX CS190 and ACL300+ were 0.51 and 0.59 U/ml, respectively, while for Stachrom Heparin they were 0.55 and 0.67 anti-Xa U/ml. We conclude that different chromogenic anti-Xa methods do not give equivalent anti-Xa levels for the same samples. Moreover, the differences are clinically significant. This is not explained entirely by instrumentation effects. Recommended therapeutic ranges may need to be method and instrument specific.

Acute and chronic alcohol-cocaine interactions in rats.

The widespread combined use of alcohol and cocaine across the United States underscores the importance of understanding how the actions of those two agents interact upon important physiological regulatory processes. In an experiment exploring acute ethanol-cocaine interactions, 16 rats were given 2.0 g/kg (IP) doses of ethanol at time zero. Two hours later, half of the rats were given cocaine (20 mg/kg, IP), while the other half were given injections of saline. The group given cocaine displayed a prolongation of the hypothermia condition induced by ethanol injection. In a chronic experiment, three groups of rats (n = 6-8) were exposed for an 11-day period to daily IP injections of 10 mg/kg cocaine, 20 mg/kg of cocaine, or saline. On day 12 these groups did not differ in their response to loss of the righting reflex induced by a 3.0 g/kg dose of ethanol. However, recovery from ethanol hypothermia was more rapid in the rats exposed to chronic cocaine. In summary, these initial studies provide evidence for exacerbation of the acute hypothermic effects of ethanol when a cocaine challenge is given 2 h after ethanol. In contrast, ethanol hypothermia was observed to be reduced when tested on day 12 after an 11-day chronic regimen of cocaine. Other dosage regimens and response measures need to be tested to understand the full scope of acute and chronic cocaine-ethanol interactions and the possible health consequences.

Body weight does not predict for anti-Xa levels after fixed dose prophylaxis with enoxaparin after orthopedic surgery.

Enoxaparin after joint arthroplasty is effective prophylaxis against venous thromboembolism. This is usually given as a fixed dose without monitoring of anti-Xa levels. This study assesses the relationship between trough anti-Xa levels, body weight, and venous thromboembolism. Consenting patients at three institutions were treated with Enoxaparin 30 mg subcutaneously bis in die postoperatively until discharge. Chromogenic anti-Xa levels were measured on the fifth postoperative day by the method of Stachrome (Diagnostica Stago). All patients had bilateral compression doppler ultrasonography on day 10 or discharge and were followed for 12 weeks for evidence of venous thromboembolism. Eleven patients developed objectively confirmed venous thromboembolism during the study. In this study, there was poor correlation between weight and anti-Xa levels. In addition, body weight and anti-Xa levels of patients who developed venous thromboembolism were compared to those who did not and there were no significant differences between the two groups. In conclusion, this study shows that there is poor correlation of trough anti-Xa levels with body weight. Recognizing the low overall event rate this study does not support the need to monitor anti-Xa levels or adjusting the dose according to weight.